Protein Wnt-3a (full name: Wnt family member 3A) (WNT3A)

Wnt3a is a highly conserved, cysteine-rich secreted glycoprotein belonging to the Wingless-type MMTV integration site (Wnt) family, which consists of 19 vertebrate members. It is a 44 kDa protein containing 24 conserved cysteine residues and spanning amino acids 19-352 in its mature form. The protein undergoes critical post-translational modifications including N-linked glycosylation at two sites (Asn87, Asn298) and palmitoleoylation at Ser209, both of which are essential for proper secretion and biological activity. Wnt3a functions as a ligand for Frizzled family seven-transmembrane receptors in conjunction with LRP5 or LRP6 co-receptors, triggering the canonical Wnt/beta-catenin signaling pathway. Upon binding, it stabilizes intracellular beta-catenin levels, leading to nuclear translocation and activation of TCF/LEF transcription factors that drive expression of Wnt target genes. The protein requires Wntless (WLS) for secretion, and structural studies have revealed how Wnt3a interacts extensively with WLS through multiple interfaces including distinct hairpin and loop regions. Wnt3a shares 96% amino acid identity with mouse Wnt3a and 87% identity with the closely related human WNT3 protein. During embryonic development, Wnt3a is essential for hippocampus formation, anterior-posterior body patterning, somite development, and proper neural tube morphogenesis. It promotes self-renewal of hematopoietic, neural, and embryonic stem cells, and is critical for maintaining intestinal crypt stem cells in the colon. Aberrant Wnt3a signaling is associated with various cancers and developmental disorders.

Other names

Wnt-3aWNT3AWnt family member 3AProto-oncogene Int-4 (for the related Wnt-3 protein)Wingless-type MMTV integration site 3A

Ligand binding to Frizzled family receptors and LRP5/6 co-receptors Stabilization of intracellular beta-catenin levels Beta-catenin binding to TCF/LEF transcription factors leading to target gene expression Requires Wntless (WLS) protein for secretion from cells Activity dependent on post-translational modifications (palmitoleoylation at Ser209 and N-linked glycosylation)